Since the publication of the article by Rettig et al1reporting the association between the human herpesvirus-8 (HHV-8) and multiple myeloma, a controversy has arisen over the implication of this new virus in the pathogenesis of plasmocytic diseases.

If the facts initially presented by Rettig et al and then by Said et al2 from the same group, on the presence of the HHV-8 genome in dendritic cell cultures and in medullary biopsy specimens of patients having multiple myeloma or Waldenström’s macroglobulinemia, are convincing, other teams using similar techniques have not all reproduced these results. In our center, we have not been able to detect any trace of viral DNA by polymerase chain reaction in any of 10 patients with multiple myeloma using the medullary cell culture used by Rettig.

The serological studies performed up to the present have argued against a role of HHV-8; no increase in its seroprevalence among patients with plasmocytic diseases has been found in essentially all of the published literature.34 This absence of anti–HHV-8 antibodies could, however, be due to immune deficiency existing in these patients.

There is a strong presumption that this virus is, at least in part, transmitted sexually. Its epidemiology may resemble that of HSV-25; at least one case of heterosexual transmission has been reported in a human immunodeficiency virus (HIV)-infected couple in which the husband had Kaposi’s sarcoma (KS) and the wife multicentric Castleman’s disease.6 Recently, a sero-epidemiological study conducted in Sardinia7 showed a high HHV-8 prevalence (39%) among relatives of patients with classic KS.

If HHV-8 plays a role in plasmocytic diseases and if the absence of seropositivity among patients is due to their immune deficient state, then one should be able to find an increase in the prevalence of HHV-8 seropositivity among their spouses.

We have thus investigated, with the written consent of patients and their partners and approval by the hospital ethics committee, the antibodies to HHV-8 among 18 partners of patients with multiple myeloma (n = 17) or Waldenström’s macroglobulinemia (n = 1). The mean age of patients was 61 years (range, 43 to 80) and 60 years for the partners (range, 42 to 78). Mean duration of living together was 35 years. None of the partners had an abnormality in plasma protein electrophoresis or detectable monoclonal Ig on immunofixation.

Serodetection was obtained by immunofluorescence assay using independently two cell lines infected by HHV-8 and not by Epstein-Barr virus (BCP-1 and BC-3). A preliminary saturation step was performed with fetal calf serum, diluted and depleted of complement, before each serum sample was tested at a dilution of 1:10. Immunostaining was then realized using fluorescent F(ab′)2 anti-human IgG fragments (Immunotech, Marseille, France).

With this methodology, HHV-8 antibodies were detected in 83% of HIV-infected patients with KS and in 10 patients (9 HIV-infected, 1 HIV−) of 10 tested (100%) with multicentric Castleman’s disease linked with HHV-8. The seroprevalence, in our area, found among a sample population of 100 blood donors was 2%.

None of the 18 patients tested nor any of the 18 partners was found to have a positive serology for HHV-8.

These results argue against the responsibility of the patients’ decreased humoral response in the lack of detectable antibody against HHV-8. If this were the case, one would expect to find a certain number of instances of transmitted infection among the partners, detectable by the serological tests, as found in Sardinia.7 Said et al8 also suggested that variations of HHV-8 encoding proteins between different strains may explain the lack of serological response detected in myeloma patients using a single HHV-8 antigen. Our study, using whole virus in infected cell lines as antigens for serological tests, renders this statement unlikely.

Thus, two hypotheses could explain the negativity of serological tests in our study as well as in previous studies: (1) absence of HHV-8 infection; (2) infection by a strain of HHV-8 associated with myeloma that could be different from those encountered in KS or Castleman’s disease and target to bone marrow dendritic cells. This infection of bone marrow dendritic cells should then specifically inhibit the normal antiviral humoral response against HHV-8.